PCCs have a significantly faster time to correction of INR and clinical achievement of hemostasis

Despite increasing use and popularity of PCCs, the ideal dose has not been established

The approved dose on the packet insert is based on the patients INR upon presentation and body weight

Other dosing regimens have been studied based upon:

Body weight alone

Indication for administration

Fixed lower doses

No regimen has been shown to be superior or has emerged as the standardized dose

A potential benefit of fixed dose protocol is that there is no delay because one does not have to wait for an INR value to return

At Hennepin County Medical Center (HCMC), a new protocol was instituted:

Initial dose of 4-factor PCC administered was a fixed dose of 1500 IU

Given to all adults needing reversal regardless of initial INR, weight, or indication

Dose chosen based off of prior study that used 1000 IU, but higher dose used because of the expected higher patient weights in our region

Study Design and Methods:

Retrospective review of patients who received 1500 IU of 4-factor PCC for emergent warfarin reversal at HCMC

Inclusion criteria: those who received 4-factor PCC at the fixed dose of 1500 IU for emergent reversal of oral anticoagulation for any indication regardless of initial INR between March 2014 and January 2015

Exclusion criteria:

No post PCC administration INR value available

Age younger than 18

Acute overdoses of oral anticoagulation

Chart review was completed to collect various data points

Purpose of Study: evaluate the experience at HCMC of using a fixed dose protocol of PCC for reversal of oral anticoagulation including safety, cost, and efficacy

Results:

41 patient received 4-factor PCC during study period

2 excluded because no post PCC INR value was available

39 patients included in study

Most cases received PCC in the ED

The most common indication was intracranial hemorrhage

92.3% received vitamin K as well

28.2% received FFP as well

Median presenting INR: 3.3

Median post-INR: 1.4

Median time to obtaining post-INR: 51 minutes

92.3% had successful INR reversal (target INR <2.0)

71.8% had successful INR reversal (target INR <1.5)

No thrombotic events within 7 days of administration of PCC

76.9% survived to hospital discharge

Of those that did not survive, 7 succumbed to uncontrolled hemorrhage

Median cost was $2264 per patient

Median cost per patient of dosing based off of packet insert would have been $2845, leading to a total reduced cost of $40,273 during the study period

Study Limitations:

Retrospective study

Relatively small cohort (39 patients)

No control group

Many received FFP and vitamin K in addition to PCC

Included those patients whose initial INR was <2.0

Used INR reversal as primary indicator of efficacy, not overall hemostatsis

Bottom Line: There is potentially a good efficacy and safety profile when using a fixed dose of PCC at 1500 IU, however, larger trials using control groups still need to be carried out.